MAPT and Atrophy: This gene-dose effect likely reflects the fact that Alzheimer's disease pathology (i.e. amyloid and tau) begins to accumulate at an earlier age among ɛ4 carriers compared to non-carriers, with ɛ4 homozygous individuals showing the youngest age of onset of amyloid accumulation and amyloid positivity, followed ɛ4 heterozygous individuals, and then ɛ4 non-carriers.98-100 It is hypothesized that this earlier age of amyloid accumulation likely initiates an earlier onset of AD-related atrophy in selected brain regions.